How I Treat Multidrug-Resistant Infections

Multidrug-resistant bacterial infections are a growing problem in veterinary practice and result in increased costs of treatment, emotional distress for pet owners, and poor outcomes such as limb amputation, organ failure or death or euthanasia.

Before treating a multidrug-resistant bacterial infection, the following questions should be asked.

1.  Is this organism that was cultured likely to be the cause of an infection? (i.e., should I even treat this organism?)

Once a positive culture has been obtained, the veterinarian must consider the significance of the positive test result. The detection of bacterial organisms within a sample does not always imply that the organism is causing the animal's clinical signs. Often times, 'multidrug-resistant infections' are treated with expensive antimicrobials when infection is not present in the first place. Contamination is the most common cause of false-positive cultures. Isolation of only one or two colonies of coagulase-negative staphylococci, Bacillus spp., Corynebacterium spp., and propionibacteria commonly suggest contamination. Isolation of large numbers of a single type of bacteria from a normally sterile site is generally clinically significant, especially when supported by cytologic examination of a stained smear that demonstrates the presence of bacteria within leukocytes. Open wounds are often contaminated with bacteria, but rarely do these go on to cause infection. Positive cultures from open wounds should only be considered significant if there is clinical evidence of infection (pus, marked erythema, fever, foul odor). In general, bacteria isolated from the urine of an animal without signs of urinary tract disease are not significant clinically and should not be treated.

2.  Are any of the drugs shown as "susceptible" the appropriate drugs for treatment of the bacterial species cultured?

Laboratories often (but not always) report results for specific antimicrobials on the basis of the organism being tested (e.g., cephalosporins may not be reported for enterococci because of intrinsic resistance). Certain antimicrobials should be generally reserved for treatment of multiple-drug resistant organisms that cause life-threatening infections (e.g., vancomycin, linezolid, meropenem).

3.  Assuming the drugs are active against the bacterial species isolated, are the drugs the right drugs for the patient in question?

Will they achieve adequate concentrations at the site of infection? What route of administration is necessary and can the antimicrobials be administered by the route that is most appropriate for my patient? Could adverse drug reactions occur in this patient with these antimicrobials? Could drug interactions occur in this patient with these antimicrobials?

For infections in sites such as the CNS, the clinician needs to consider whether or not an antimicrobial to which the organism is reported as susceptible will penetrate that site. The clinician should also consider other factors, such as immunosuppression, pregnancy and other concurrent illness or drug therapy, when treating infections on the basis of antimicrobial susceptibility test results.

4.  Is the antimicrobial drug currently being administered the most appropriate for the infection I am trying to treat?

Because antimicrobial susceptibility testing results are generally not available until 2–3 days after submission of a specimen for culture, in animals that are critically ill, antimicrobial therapy may already have been initiated by the time those results are available. The susceptibility results may show that the organism is resistant to a drug being used, in which case the drug should be changed to one that the organism is susceptible to. The susceptibility pattern can also aid in choosing an alternate drug when the patient does not tolerate the initial drug prescribed. Susceptibility testing may indicate that the organism is susceptible to a more narrow­spectrum (and generally less expensive) antimicrobial drug than the drug initially prescribed, in which case the treatment should be changed to minimize the development of antimicrobial resistance.

5.  Can I shorten the duration of therapy?

Currently there is a trend to try to shorten the duration of therapy to minimize selection pressure on bacterial populations. This differs from previous recommendations to 'finish a course' of antimicrobial drugs. In general, surgical prophylaxis should involve administration of antimicrobials only in the immediate perioperative period (immediately before and during surgery).

6.  What is the underlying problem predisposing to infection?

Bacterial infections are rarely primary problems and usually there is an underlying predisposing disorder, such as laryngeal paralysis or chronic bronchitis (pneumonia), allergic skin disease (pyoderma), a foreign body, recessed vulva, or diabetes mellitus. Identification and management of the underlying problem to the best extent possible is critical to minimize recurrence of infection following antimicrobial drug therapy. In some cases, the underlying disorder cannot be effectively treated, and the clinician needs to decide to what extent treatment of secondary bacterial infections is necessary.

7.  Are there non-antimicrobial alternatives to treating the problem?

Increasingly non-antimicrobial alternatives are used for treatment of resistant bacterial infections. These include frequent bathing for canine superficial pyoderma, and live biotherapeutic products for urinary tract infections. Topical antimicrobial drugs overwhelm bacterial resistance mechanisms and may be useful for focal pyoderma or bacterial otitis externa.